Immunogenicity of Moraxella catarrhalis vaccine candidates in children Abstract Moraxella catarrhalis (Mcat) is a bacterium causing more than 100 million cases of acute otitis media (AOM) in children worldwide and up to 3 million cases of acute exacerbations of chronic obstructive pulmonary disease in adults in the United States annually. There is no vaccine available to prevent Mcat infection. Our group has identified a subset of children who are stringently-defined otitis prone (sOP) that display low or absent antibody responses to most but not all vaccine candidate proteins of two leading bacteria responsible for AOM, nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (Spn). The immunologic mechanisms of these defects in sOP children are under intensive investigation in our laboratory (R01 DC08671). We propose to evaluate the age-dependent immunogenicity of and functional antibody response to 4 Mcat vaccine candidate proteins elicited by natural exposure to Mcat in sOP and non-otitis prone (NOP) children 6-36 months of age. Our central hypothesis is that detection of Mcat-specific functional antibodies is most effective in evaluating vaccine candidates with the greatest promise for clinical development. Therefore, we will (1) assess serum and mucosal antibody responses to Mcat nasopharyngeal (NP) colonization; (2) assess serum and mucosal antibody responses at onset of and after recovery from Mcat-caused AOM (3) analyze the correlative relationship between the serum and mucosal antibody responses and NP colonization and AOM rates; and (4) analyze the correlative relationship among the natural antibody responses to Mcat vaccine candidates. By comparing the immune responses between sOP and NOP children, we will identify those antigens that are highly immunogenic in sOP children. Use of these antigens in a vaccine, may lead to effectively raising the antibody response to a protective level against Mcat-caused recurrent AOM. We will determine those Mcat antigens that elicit synchronous antibody responses and therefore would be less likely to produce diminished antibody response caused by antigenic competition and interference in a multi-component vaccine. Overall, our study will help to identify Mcat antigens with the best potential in a multivalent vaccine to protect against AOM.